RGD Reference Report - Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure. - Rat Genome Database

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Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure.

Authors: Brushia, RJ  Walsh, DA 
Citation: Brushia RJ and Walsh DA, Front Biosci. 1999 Sep 15;4:D618-41.
RGD ID: 2305981
Pubmed: PMID:10487978   (View Abstract at PubMed)

Intracellular glycogen stores are used to maintain blood-glucose homeostasis during fasting, are a source of energy for muscle contraction, and are used to support a broad range of cellular activities in most tissues. A diversity of signals accelerate glycogen degradation that are mediated by phosphorylase b kinase (Phk), which phosphorylates and thereby activates glycogen phosphorylase. Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit. Ca2+ relieves inhibition via the delta subunit, which is identical to calmodulin but remains an integral component of the holoenzyme even when the [Ca2+] is lowered to nanomolar levels. Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme. The stimulatory effects of Ca2+ and phosphorylation appear to be structurally coupled and are cooperative. In addition, Phk is activated in vitro by autophosphorylation, limited proteolysis of the regulatory subunits, and various allosteric effectors and these may also be mechanisms of physiological importance. The molecular mechanisms of regulation are currently poorly understood, but new insights are beginning to emerge. This review discusses current knowledge and concepts of the structure, function and regulation of Phk.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CALM1Humanglycogen degradation pathway   TAS  RGD 
CALM2Humanglycogen degradation pathway   TAS  RGD 
CALM3Humanglycogen degradation pathway   TAS  RGD 
Calm1Ratglycogen degradation pathway   ISOCALM1 (Homo sapiens) RGD 
Calm1Mouseglycogen degradation pathway   ISOCALM1 (Homo sapiens) RGD 
Calm2Ratglycogen degradation pathway   ISOCALM2 (Homo sapiens) RGD 
Calm2Mouseglycogen degradation pathway   ISOCALM2 (Homo sapiens) RGD 
Calm3Ratglycogen degradation pathway   ISOCALM3 (Homo sapiens) RGD 
Calm3Mouseglycogen degradation pathway   ISOCALM3 (Homo sapiens) RGD 
PHKA1Humanglycogen degradation pathway   TAS  RGD 
PHKA2Humanglycogen degradation pathway   TAS  RGD 
PHKBHumanglycogen degradation pathway   TAS  RGD 
PHKG1Humanglycogen degradation pathway   TAS  RGD 
PHKG2Humanglycogen degradation pathway   TAS  RGD 
Phka1Ratglycogen degradation pathway   ISOPHKA1 (Homo sapiens) RGD 
Phka1Mouseglycogen degradation pathway   ISOPHKA1 (Homo sapiens) RGD 
Phka2Mouseglycogen degradation pathway   ISOPHKA2 (Homo sapiens) RGD 
Phka2Ratglycogen degradation pathway   ISOPHKA2 (Homo sapiens) RGD 
PhkbRatglycogen degradation pathway   ISOPHKB (Homo sapiens) RGD 
PhkbMouseglycogen degradation pathway   ISOPHKB (Homo sapiens) RGD 
Phkg1Ratglycogen degradation pathway   ISOPHKG1 (Homo sapiens) RGD 
Phkg1Mouseglycogen degradation pathway   ISOPHKG1 (Homo sapiens) RGD 
Phkg2Ratglycogen degradation pathway   ISOPHKG2 (Homo sapiens) RGD 
Phkg2Mouseglycogen degradation pathway   ISOPHKG2 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Calm1  (calmodulin 1)
Calm2  (calmodulin 2)
Calm3  (calmodulin 3)
Phka1  (phosphorylase kinase regulatory subunit alpha 1)
Phka2  (phosphorylase kinase regulatory subunit alpha 2)
Phkb  (phosphorylase kinase regulatory subunit beta)
Phkg1  (phosphorylase kinase catalytic subunit gamma 1)
Phkg2  (phosphorylase kinase catalytic subunit gamma 2)

Genes (Mus musculus)
Calm1  (calmodulin 1)
Calm2  (calmodulin 2)
Calm3  (calmodulin 3)
Phka1  (phosphorylase kinase alpha 1)
Phka2  (phosphorylase kinase alpha 2)
Phkb  (phosphorylase kinase beta)
Phkg1  (phosphorylase kinase gamma 1)
Phkg2  (phosphorylase kinase, gamma 2 (testis))

Genes (Homo sapiens)
CALM1  (calmodulin 1)
CALM2  (calmodulin 2)
CALM3  (calmodulin 3)
PHKA1  (phosphorylase kinase regulatory subunit alpha 1)
PHKA2  (phosphorylase kinase regulatory subunit alpha 2)
PHKB  (phosphorylase kinase regulatory subunit beta)
PHKG1  (phosphorylase kinase catalytic subunit gamma 1)
PHKG2  (phosphorylase kinase catalytic subunit gamma 2)


Additional Information